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We are analyzing https://www.nature.com/articles/s41388-018-0138-y.

Title:
Targeting UDP-α-d-glucose 6-dehydrogenase inhibits glioblastoma growth and migration | Oncogene
Description:
UDP-glucose 6-dehydrogenase (UGDH) produces UDP-α-d-glucuronic acid, the precursors for glycosaminoglycans (GAGs) and proteoglycans of the extracellular matrix. Elevated GAG formation has been implicated in a variety of human diseases, including glioblastoma (GBM). In our previous study, we found that Krüppel-like factor 4 (KLF4) promotes GBM cell migration by binding to methylated DNA, mainly methylated CpGs (mCpG) and transactivating gene expression. We identified UDGH as one of the downstream targets of KLF4–mCpG binding activity. In this study, we show that KLF4 upregulates UGDH expression in a mCpG-dependent manner, and UGDH is required for KLF4-induced cell migration in vitro. UGDH knockdown decreases GAG abundance in GBM cells, as well as cell proliferation and migration in vitro. In intracranial xenografts, reduced UGDH inhibits tumor growth and migration, accompanied by a decrease in the expression of extracellular matrix proteins such as tenascin C, brevican. Our studies demonstrate a novel DNA methylation-dependent UGDH upregulation by KLF4. Developing UGDH antagonists to decrease the synthesis of extracellular matrix components will be a useful strategy for GBM therapy.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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  • Education
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$63,100 per month
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Keywords {🔍}

pubmed, article, google, scholar, cas, nature, cancer, central, glioblastoma, cell, ugdh, access, migration, xia, extracellular, nih, usa, supplemental, content, oncogene, dehydrogenase, lal, laterra, wang, matrix, cells, department, medicine, cookies, growth, wei, factor, binding, baltimore, school, figure, privacy, inhibits, oyinlade, john, udpglucose, klf, promotes, dna, tumor, res, research, johns, hopkins, data,

Topics {✒️}

nature portfolio produces udp-α-d-glucuronic acid permissions reprints moser research institute privacy policy nature advertising udp-glucose dehydrogenase social media author information authors development author correspondence klf4-induced cell migration klf4–mcpg binding activity personal data springerlink instant access data protection hepatocyte growth factor permissions inducing dna damage integrin alpha6 inhibition cancer cell biology transactivating gene expression mcpg-dependent manner promotes glioblastoma invasion inhibits glioblastoma stemness fibroinflammatory tumor microenvironment dna binding proteins tumor-propagating stem developing ugdh antagonists privacy human transcription factors elevated gag formation indiana university school tumor microenvironment tenascin global transcription repression cell adhes migr migration olutobi oyinlade article oyinlade explore content subscription content extracellular matrix proteins extracellular matrix components extracellular matrix microenvironment extracellular matrix degradation european economic area institutional subscriptions read sugar nucleotide clearance potential drug target biochem soc trans

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